The current study aimed to prepare a topical gel containing solid lipid nanoparticles (SLNs) encapsulating fluoxetine for diabetic wound healing effects. Fluoxetine (FX) was loaded into SLNs by employing an emulsion solvent evaporation technique using stearic acid as a lipid, and soya lecithin as a surfactant. SLNs were then evaluated for particle size, polydispersity index (PDI), zeta potential (ZP), percent entrapment efficiency (%EE), percent drug loading (%DL), and in vitro drug release. The optimized SLN (FS3) composed of FX (100 mg), SA (150 mg), and SA (100 mg) displayed mean particle size (467.3 ± 2.2nm), PDI (0.435 ± 0.02), ZP (−32.2 ± 4.47mV), EE (95.8 ± 3.38%), and DL (16.4 ± 2.4%). FTIR and DSC studies denote drug-polymer compatibility and the amorphous nature of FX in the SLNs. The drug release at 24 h was found to be (98.89 ± 2.57%) which followed the fickian diffusion mechanism. SLN (FS3) was further loaded into carbopol gel and tested for pH, spreadability, and extrudability of pharmaceutical parameters. In-vitro release of FX from the SLN gel and plain gel was compared, diabetic wound healing gel (DWH) showed sustained drug delivery. An in vivo study was also performed for DWH gel in streptozotocin-induced diabetic rats. Histopathological examination exhibited DWH gel-treated wounds have increased hydroxyproline, cellular proliferation, a rise in the number of blood vessels, and the level of collagen synthesis. Thus, DWH gel-loaded SLN encapsulated with FX could be a potential carrier for the effective treatment and management of diabetic wounds.
